How is "Broadly-defined Headache" encoded by the genome?
A headache is one of the most common neurological symptoms, with a prevalence of over 90% in the general population in the UK. According to the International Headache Society, headaches can be generally divided into two categories—primary headaches, if not associated with another disorder, and secondary headache, if associated with an underlying medical illness. Primary headaches mainly include migraine, tension-type, and cluster headaches. Secondary headaches include any head pain caused by infection, neoplasm, head injury, metabolic disorders, or drugs. Tension-type headache is the most prevalent type of headache, whereas migraine is the most disabling.
Family and twin studies have suggested that migraine and tension-type headaches are heritable traits with a heritability of over 40%. Recently, genome-wide association studies (GWAS) have identified many genetic loci associated with migraine. A GWAS meta-analysis of 375,000 patients involving 22 centers has identified 38 genetic susceptibility loci for migraine, with the LRP1 region in chromosome 12 being the most strongly associated. Along with other GWAS on migraine, the total number of loci associated with migraine is currently 47.
But before this study, no GWAS had been performed for tension-type headaches. Researchers used the UK Biobank cohort to identify the genetic variants associated with headaches, including migraine and tension-type headaches. The UK Biobank participants were offered a pain-related questionnaire, which included the question: ‘in the last month, have you experienced any of the following that interfered with your usual activities?’. The options were: 1. Headache; 2. Facial pain; 3. Neck or shoulder pain; 4. Back pain; 5. Stomach or abdominal pain; 6. Hip pain; 7. Knee pain; 8. Pain all over the body; 9. None of the above; 10. Prefer not to say. Participants could select more than one option. The headache cases in this study were those who selected the ‘Headache’ option for the above question, regardless of whether they had selected other options. The controls in this study were those who selected the ‘None of the above’ option. 3343 SNPs showed a significant relationship with broadly-defined headaches in 223,773 participants (74,461 cases and 149,312 controls). The study found significant relationships between brain tissues and genetic associations and identified significant positive genetic correlations between headaches and many psychological traits.
The main limitation of the study is that it was solely based on a survey, that did not ask for any information about the headache severity nor provide subgrouping opportunities such as differentiating migraine from tension-type headache or secondary headache types. In the future, more detailed and focused phenotyping will be generated. Read more about the study here:
https://pubmed.ncbi.nlm.nih.gov/29397368/
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